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Query: UMLS:C0149521 (chronic pancreatitis)
 7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary chronic pancreatitis (HCP) is a very rare form of early-onset chronic pancreatitis. Apart from young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. Diagnostic criteria and treatment of HCP also resemble those of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile-duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, the disease is mild in most patients. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation, disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes--such as the anionic trypsinogen (PRSS2), the serine protease inhibitor Kazal type 1 (SPINK1), and the cystic fibrosis transmembrane conductance regulator (CFTR)--have also been found to be associated with chronic pancreatitis (idiopathic and hereditary). Genetic testing should only be performed in carefully selected patients by direct DNA sequencing, and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications such as pseudocysts and bile-duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. The risk of pancreatic cancer is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.
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PMID:Hereditary chronic pancreatitis. 1820 17

(Table is included in full-text article.)Cystic fibrosis (CF) is the most frequent cause of exocrine pancreatic insufficiency in childhood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes CFTR protein that functions as cyclic AMP-dependent chloride channel allowing the passage of anions and secondarily water into the lumen of pancreatic ducts. Luminal chlorides are exchanged for bicarbonates. The lack of CFTR channel or its disrupted function (being the consequence of CFTR gene mutations) results in reduced volume of more acidic secretion. It has been suggested that such a situation leads to the precipitation of highly concentrated protein-containing secretion with obstruction and organ damage. The intensity of this process determines the progression of the disease. Steatorrhea is the significant symptom of classical form of CF. Residual pancreatic secretion in a subset of patients, however, allows for normal lipid digestion and absorption. Previous cross-sectional clinical studies estimated that about 85-90% of CF patients in preschool, school and older age are pancreatic insufficient. More frequent detection of mild and nonclassic forms of CF leads to higher frequency of pancreatic sufficiency (PS). The potential decline of exocrine pancreatic function, however, should be always considered. All PS patients with at least one severe or unknown CFTR mutation should be longitudinally assessed for the progression of pancreatic dysfunction. Recurrent acute and chronic pancreatitis is not a rare clinical condition in PS patients with PS: it might be the presenting symptom, even preceding CF diagnosis by several years. Potential appearance of this complication in individuals with pancreatic insufficiency demands elucidation.
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PMID:The changing face of the exocrine pancreas in cystic fibrosis: pancreatic sufficiency, pancreatitis and genotype. 1830 Dec 94

High-resolution melting analysis of polymerase chain reaction products for mutation scanning, which began in the early 2000s, is based on monitoring of the fluorescence released during the melting of double-stranded DNA labeled with specifically developed saturation dye, such as LC-Green. We report here the validation of this method to scan 98% of the coding sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We designed 32 pairs of primers to amplify and analyze the 27 exons of the gene. Thanks to the addition of a small GC-clamp at the 5' ends of the primers, one single melting domain and one identical annealing temperature were obtained to co-amplify all of the fragments. A total of 307 DNA samples, extracted by the salt precipitation method, carrying 221 mutations and 21 polymorphisms, plus 20 control samples free from variations (confirmed by denaturing high-performance liquid chromatography analysis), was used. With the conditions described in this study, 100% of samples that carry heterozygous mutations and 60% of those with homozygous mutations were identified. The study of a cohort of 136 idiopathic chronic pancreatitis patients enabled us to prospectively evaluate this technique. Thus, high-resolution melting analysis is a robust and sensitive single-tube technique for screening mutations in a gene and promises to become the gold standard over denaturing high-performance liquid chromatography, particularly for highly mutated genes such as CFTR, and appears suitable for use in reference diagnostic laboratories.
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PMID:Validation of high-resolution DNA melting analysis for mutation scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. 1868 95

DNA analyses of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in Japanese patients with idiopathic chronic pancreatitis (ICP) were performed to determine the relationship between the CFTR mutation and ICP. The study included patients with alcoholic pancreatitis (n = 20), patients with ICP (n = 20) and healthy volunteers (controls; n = 110). The poly-T region in intron 8 of the CFTR gene was analysed by direct sequencing. The CFTR coding region was screened using single-strand conformational polymorphism and direct sequencing. In the controls, frequencies of the 5T genotype and 5T allele were 4.5% and 3.6%, respectively. The frequency of the 5T genotype was significantly higher in the ICP group (20%) versus controls, but was not significantly different in alcoholic chronic pancreatitis patients (5%). Thus, the CFTR gene mutation, especially the 5T genotype, appears to have some relationship to ICP prevalence in Japanese patients independent of cystic fibrosis.
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PMID:Impact of cystic fibrosis transmembrane conductance regulator gene mutation on the occurrence of chronic pancreatitis in Japanese patients. 1938 31

Chronic pancreatitis (CP) is a persistent inflammation of the pancreas. Over the past 12 years, genetic studies of hereditary, familial, and idiopathic forms of CP have made great progress in defining the disease pathogenesis. Identification of gain-of-function missense and copy number mutations in the cationic trypsinogen gene (PRSS1) and loss-of-function variants in both the pancreatic secretory trypsin inhibitor (SPINK1) and chymotrypsinogen C (CTRC) genes has firmly established the pivotal role of prematurely activated trypsin within the pancreas in the etiology of CP. Loss-of-function variants in the cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-sensing receptor (CASR) genes also increase the risk of CP. Here, we review recent developments in this rapidly evolving field, highlight the importance of gene-gene and gene-environment interactions in causing the disease, and discuss the opportunities and challenges in identifying novel genetic factors that affect susceptibility/resistance to CP.
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PMID:Chronic pancreatitis: genetics and pathogenesis. 1945 52

The etiopathogenesis of tropical chronic pancreatitis (TCP) remains unclear. Malnutrition, dietary toxins like cyanogens in cassava and micronutrient deficiency are proposed factors. The description and characterization of genetic factors in TCP has added a new dimension to the understanding of pathogenesis of the disease. However, there is sparse data on the association of TCP with cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We report 8 patients of TCP with CFTR gene mutations, including one with a novel mutation, and describe the clinical profile of these patients. Further prospective genetic studies on the association of CFTR gene mutations are essential in order to unravel the genetic basis of TCP.
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PMID:Genotype-phenotype correlation in 9 patients with tropical pancreatitis and identified gene mutations. 1969 93

Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical courses. Growing evidence for genetic risk and modifying factors, plus strong evidence that only a minority of patients with these disorders are heavy alcohol drinkers, has revolutionized our concept of these diseases. Once considered a self-inflicted injury, pancreatitis is now recognized as a complex inflammatory condition like inflammatory bowel disease. Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients with mutations in these genes are at increased risk of pancreatitis caused by a variety of stresses including hyperlipidemia and hypercalcemia. Multiple studies are reporting new polymorphisms, as well as complex gene x gene and gene x environmental interactions.
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PMID:Genetic aspects of pancreatitis. 2005 46

Chronic pancreatitis is a progressive fibroinflammatory disease that exists in large-duct (often with intraductal calculi) or small-duct form. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals) and genetic factors (eg, mutation in a trypsin-controlling gene or the cystic fibrosis transmembrane conductance regulator); a few patients have hereditary or autoimmune disease. Pain in the form of recurrent attacks of pancreatitis (representing paralysis of apical exocytosis in acinar cells) or constant and disabling pain is usually the main symptom. Management of the pain is mainly empirical, involving potent analgesics, duct drainage by endoscopic or surgical means, and partial or total pancreatectomy. However, steroids rapidly reduce symptoms in patients with autoimmune pancreatitis, and micronutrient therapy to correct electrophilic stress is emerging as a promising treatment in the other patients. Steatorrhoea, diabetes, local complications, and psychosocial issues associated with the disease are additional therapeutic challenges.
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PMID:Chronic pancreatitis. 2139 20

Several diseases have been clinically or genetically related to cystic fibrosis (CF), but a consensus definition is lacking. Here, we present a proposal for consensus guidelines on cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs), reached after expert discussion and two dedicated workshops. A CFTR-RD may be defined as "a clinical entity associated with CFTR dysfunction that does not fulfil diagnostic criteria for CF". The utility of sweat testing, mutation analysis, nasal potential difference, and/or intestinal current measurement for the differential diagnosis of CF and CFTR-RD is discussed. Algorithms which use genetic and functional diagnostic tests to distinguish CF and CFTR-RDs are presented. According to present knowledge, congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis and disseminated bronchiectasis, all with CFTR dysfunction, are CFTR-RDs.
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PMID:Recommendations for the classification of diseases as CFTR-related disorders. 2165 49

Genetic risk factors of chronic pancreatitis (CP) have been identified and a number of studies have found that CP can lead to pancreatic cancer. Therefore, the detection of pancreatitis-associated gene mutations can aid the pancreatic cancer diagnostic process. Mutations in three genes, the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the pancreatic secretory trypsin inhibitor (SPINK1) gene, have been identified as risk factors for CP. The aim of this study was to describe specific novel mutations in the intron of the PRSS1 gene in patients with pancreatic cancer and CP. A total of 65 unrelated patients with pancreatic cancer and 29 with CP were reviewed. Mutations and polymorphisms of the PRSS1 gene were analyzed by direct sequencing. Information regarding clinical data and smoking exposure was collected by personal interviews using a structured questionnaire. IVS 3+36 A>G mutation in the PRSS1 gene was found in 2 cases with pancreatic cancer, and these 2 patients were classified as never-smokers. IVS 3+127 T>A and IVS 3+157 G>C double mutations were identified in one patient with CP. All patients were found to have serum trypsin levels lower than that of the normal controls. Therefore, the PRSS1 gene mutation may be a special common cause of pancreatic cancer and CP.
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PMID:PRSS1 intron mutations in patients with pancreatic cancer and chronic pancreatitis. 2210 5


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